Differentiated thyroid cancer is the most common endocrine malignancy (Cady, B. and Rossi, R. L. , 1991). In the United States, there are approximately 14,000 new patients and 1,100 deaths per year (Shah, J. P. and Lydiatt, W., 1995). Follicular cancers generally metastasize via hematogenous dissemination, whereas papillary cancers spread through lymphatic involvement. Patients with distant metastatic disease have the worst prognosis (Braverman, L. E., et al., 1991).
Current techniques to detect metastases include nuclear scans (such as .sup.131 I scanning) as well as measurement of serum thyroglobulin. Detectable serum thyroglobulin levels are found in normal patients as well as some types of benign thyroid disease (LoGerfo, P., et al., 1979).
Thyroglobulin is a large glycoprotein (molecular weight of 660,000) secreted exclusively by the thyroid follicular cell and is often elevated in patients with differentiated thyroid malignancies.
Thyroid peroxidase is a membrane-bound glycosylated, hemoprotein enzyme that plays a key role in thyroid hormone biosynthesis by catalyzing both the iodination of tyrosyl residues and the coupling of iodotyrosyl residues in thyroglobulin. Until 1985, this was considered to be its only role in the thyroid; however, thyroid peroxidase is closely related to, if not identified with, the thyroid microsomal antigen associated with the antithyroid microsomal autoantibodies found in the serum of many patients with autoimmune thyroid disease.
The detection of small numbers of circulating thyroid cells has previously been impossible due to insensitive techniques. With polymerase chain reaction (PCR), however, it is now possible to utilize a tissue-specific gene expression approach to detect circulating thyrocytes. This technique has also been utilized with other solid tumors such as prostate and neuroblastoma (Moreno, J. G., et al., 1992; Katz, A. E., et al., 1994; Seiden, M. V., et al., 1994; Mattano, L. A., et al., 1992; Burchill, S. A., et al., 1994; Johnson, P. W. M., et al., 1995). Thyroglobulin and thyroid peroxidase are two examples of proteins that are expressed specifically in thyrocytes. Since it is believed that patients with thyroid cancer and metastatic thyroid cancer will have circulating thyroid cells in the peripheral bloodstream, whereas those patients without thyroid cancer will not, one could use PCR to amplify the mRNA transcripts of these proteins in order to detect circulating thyroctyes. The detection of circulating thyrocytes may have important significance in the diagnosis and prognosis of thyroid cancer.